Project Summary Dr. Jennifer A. Kim is a critical care neurologist and neuroscientist at Yale-New Haven Hospital. Her long-term career goal is to become an independently funded translational investigator with expertise in signal processing of neurophysiologic and neuroimaging data to identify early biomarkers of secondary brain injury in critically ill patients, particularly related to post-traumatic epilepsy. Post-traumatic epilepsy is a disabling complication of traumatic brain injury (TBI). There is an urgent need to find biomarkers of post-traumatic epilepsy to identify patients at high risk for developing this complication. It is a population in which early biomarker identification could improve patient monitoring and ultimately treatment development to circumvent epileptogenesis. Post- traumatic epilepsy contributes to worsening of the already high rates of TBI morbidity, disability and cost of care, thus emphasizing the importance of preventing this complication. We need to find biomarkers to best define those most likely to benefit from potential treatments and make such treatment discovery trials more feasible. During the proposed training period, the candidate will expand upon her knowledge of EEG signal processing and machine learning techniques and acquire new skills in neuroimaging analysis using Magnetic Resonance technologies and biostatistics. To accomplish this, Dr. Kim has brought together a strong mentorship team of Dr. Hal Blumenfeld (primary mentor) and co-mentors Drs. Todd Constable, Brandon Westover and Brian Edlow who have expertise in multi-modal approaches to studying epilepsy, functional MRI analysis, computational EEG analysis and structural TBI imaging, respectively. Under their mentorship, Dr. Kim proposes to: 1) quantify epileptiform abnormality (EA) frequency and identify EA waveform features that optimally predict PTE, 2) determine if direct hippocampal injury, assessed by cortical thickness and contusion volume, stratifies PTE risk 3) assess whether indirect hippocampal injury, based on structural and functional MRI connectivity analyses, portend PTE. The overall goal is to identify early biomarkers of patients at high risk for post-traumatic epilepsy to target development of anti-epileptogenesis treatments. Bringing together advanced neurophysiologic and neuroimaging analysis and this strong mentorship support, this project opens new avenues for optimizing follow-up care and advancing potential treatment development for all traumatic brain injury patients at risk for post-traumatic epilepsy. This well-defined patient-oriented research proposal, in concert with the mentorship and structured didactic curriculum, will provide Dr. Kim with the skills that are essential to develop an independent career in neurophysiological and neuroimaging research that translates to improving patient outcomes.